A Gene That Controls Hunger and Satiety (LEPR)

Exercise

Physical exercise and long-term fitness seem to decrease total leptin production and make people less likely to develop leptin resistance [R, R, R].

High-intensity exercise is probably the best strategy to lose weight. In addition to promoting fat burning, the increased norepinephrine production may suppress food intake according to a study in rats [R].

Being active burns calories and jump-starts metabolism. Some studies suggest it also increases BDNF, which supports mental health and might cause us to eat less [R].

Exercise also increases endorphins, which activates mu-opioid receptors and also suppresses appetite [R].

Aerobic exercise (like walking, running, swimming, etc) has also been shown to cause major reductions in belly fat in multiple studies [R, R].

Yoga may also be a useful tool for weight loss [R, R, R].

Physical fitness decreases total leptin production, reducing the chances of developing leptin resistance. Exercise is also a central part of any weight loss regime.

Stress Management

Leptin resistance and stress may form a feedback loop wherein each contributes to the other: people with detrimental LEPR variants may have higher baseline stress, and people under a lot of stress may be more likely to develop leptin resistance [R, R].

Stress is known to cause weight gain. Stress increases cortisol and dynorphin, both of which cause weight gain [R, R, R].

It also increases glutamate, which increases appetite, while decreases NGF and BDNF, both of which are appetite suppressants [19].

Additionally, it makes the brain resistant to serotonin, a neurotransmitter that also suppresses appetite. Stress also causes resistance to dopamine, which may cause us to eat more as we’ll need to eat more food for the same rewarding effects [R, R, R].

Psychological stress is associated with both weight gain and leptin resistance.

Improve Sleep Quantity & Quality

Multiple animal studies have suggested a close relationship between sleep and leptin.

In a mouse study, chronic jet lag disrupted the clock in fat cells and induced leptin resistance in the brain [R].

Poor sleep can increase hunger and cravings and disrupt hunger hormones like ghrelin and leptin [R, R].

Short sleep duration has been associated with weight gain in many studies. A meta-analysis of 30 studies and over 630,000 people associated short sleep duration with a 55% higher incidence of obesity in adults and 89% in children [R, R, R].

One study suggested that night-shift workers, who must be awake, active, and eating during the night seem to be at a higher risk of obesity and metabolic diseases [R].

Leptin is reliant on the sleep cycle; poor or limited sleep may induce leptin resistance and has also been associated with weight gain.

Positive Social Interactions

Leptin and oxytocin, the hormone primarily responsible for social bonding, communicate closely with one another. In fact, some researchers have considered oxytocin administration as a possible complementary treatment for leptin resistance in obese patients; however, this approach remains unproven [R, R].

Oxytocin is released by positive human interactions and has been shown to decrease hunger in multiple animal studies [R].

The experience of love also increases NGF, which reduces appetite, and increases endorphins, which activate mu-opioid receptors [R].

The “love hormone” oxytocin interacts closely with leptin and has been studied for its ability to decrease hunger.

Reducing Carbohydrates

People with potentially detrimental LEPR variants may be more likely to gain weight from eating carbohydrates [R].

In a clinical trial on 119 overweight people, a low-carbohydrate ketogenic diet was as effective as a low-fat diet for weight loss but had the advantages that it reduced appetite and negative affect. A meta-analysis of 13 studies and over 1,500 people concluded that low-carbohydrate ketogenic diets are more effective than low-fat diets for losing weight [R, R].

Polyphenol-Rich Fruits & Vegetables

In animals, the consumption of polyphenol-rich fruits and vegetables prevented leptin resistance [R].

Vegetables are rich in soluble fiber, which has been shown to cause weight loss in some studies. Fiber gets broken down by bacteria in the digestive tract to produce butyrate, which has weight loss effects in animals [R, R, R, R].

Fruits have been useful weight management foods as well. In a study of 91 obese individuals, eating half a fresh grapefruit before meals caused weight loss of 3.5 pounds (1.6 kg) over a period of 12 weeks [R].

Polyphenols from various fruits (including blueberries and apples) led to lower weight in animal studies [R, R].

Spicy Foods

Capsaicin acts on a receptor called TRPV1, the activation of which is believed to prevent leptin resistance in mice [R].

TRPV1 may also speed up the metabolism, increase energy expenditure, and reduce appetite [R, R, R, R].

When ingested orally with green tea, capsaicin reduced appetite and food intake in humans. Early research indicates that taking capsaicin as a weight loss supplement is safe, but more must be known about its effectiveness [R, R, R].

If you like spicy food, you’re in luck: capsaicin is found in chili peppers and is responsible for their spicy flavor. The spicier the pepper, the more capsaicin it contains [R, R].

Increasing polyphenol-rich fruits and vegetables, eating spicy foods, and avoiding carbohydrates may help improve leptin sensitivity.

Berberine

Berberine supplementation reduced BMI and enhanced leptin sensitivity in 37 patients with metabolic syndrome. In another study, it caused an average weight loss of 5 lbs (2.3 kg) and lowered blood lipids [R, R].

According to a 2020 review of human and animal studies, berberine might contribute to weight loss by improving gut microbiota and glucose and fat metabolism [R].

Yerba Mate

In mice, yerba mate appeared to prevent leptin resistance. Its effect on leptin in humans has gone largely unstudied, though some research suggests that it may be useful as a weight management tool [R].

Supplementation with yerba mate (3 g/day for 12 weeks) reduced body fat mass, body fat percentage, and waist-hip ratios of 30 obese participants, with no adverse side effects [R].

Yerba mate supplementation (1,000 mg) before exercise increased fat metabolism (fatty acid oxidation) and the energy used metabolizing the fat (crossover study with 14 healthy participants) [R].

In a mouse study, yerba mate supplementation decreased food intake and energy use and reduced the levels of cholesterol, triglycerides, and sugar in the blood. Additionally, it reduced the accumulation of fat in mice fed a high-fat diet [R].

Probiotics

Some probiotic supplements (including L. rhamnosus) improved leptin resistance in obese mice which had been fed a high-fat diet [R].

In a clinical trial of 125 obese adults, L. rhamnosus induced weight loss, reduced fat mass, and reduced circulating leptin [R].

Additionally, L. rhamnosus CGMCC1.3724 improved liver parameters in a small trial of 20 obese children with liver dysfunction noncompliant with lifestyle interventions [R].

Berberine, yerba mate, and L. rhamnosus probiotics have been found to improve leptin resistance and promote weight loss in some studies.

Garcinia

In studies on obese animals, Garcinia cambogia extract enhanced glucose metabolism and leptin signaling [R, R, R].

In a clinical trial on 99 obese men, it lowered BMI and belly fat when combined with a weight-loss drug (orlistat) [R].

Garcinia reduced body weight and fat mass in many clinical trials, ranging from 21 to 100 overweight and obese subjects [R, R, R, R, R, R].

In a 2011 review of 12 studies, Garcinia extract caused a weight loss of about 2 pounds (0.88 kg) over several weeks [R].

Garcinia cambogia extract may counteract your variant by improving leptin resistance. It supported weight loss in many smaller clinical trials.

Metformin is a drug frequently prescribed to people with diabetes or PCOS to help regulate the metabolism. In women with PCOS, metformin has been shown to restore sensitivity to leptin [R].

Metformin decreased food consumption and induced weight loss in a clinical trial on 12 obese women with type 2 diabetes. Metformin may help you lose weight if you have type 2 diabetes and your doctor prescribes you this medication. You may discuss with your doctor if it may be recommended in your case [R].

Metformin is a prescription medication that should never be taken without the express instruction and supervision of a doctor.